Introduction Existing trials show limited effectiveness of school-based sexual health interventions (SBSHI) in preventing sexually transmitted infections (STI) including HIV in sub-Saharan Africa (sSA). Limitations in content, implementation or evaluation are some reasons for this limited effectiveness. We explored facilitators and challenges to designing, implementing and evaluating SBSHI in sSA.

Methods We conducted 27 semi-structured interviews with purposeful sample of researchers who have developed, implemented or evaluated SBSHI in sSA. Interviews were audio recorded, transcribed verbatim and analysed thematically. Intervention Mapping framework (IM) was used to organise emerging themes.

Results Participants are experts in SBSHI in sSA with experiences ranging between 2–30 years. We identified 33 themes that mapped onto the six steps of IM. During development, social factors such as poverty and school infrastructures including quality of teaching, in addition to sexual health needs, should be addressed. SBSHI should be culturally sensitive, address inter-generational and open communications on sexual issues, and clearly state aims to avoid any misunderstanding. Curriculum should also address contemporary issues in HIV prevention (Treatment as Prevention, Pre-exposure Prophylaxis, Voluntary Medical Male Circumcision and Gender-Based Violence). During implementation, SBSHI should be prepared for oppositions at various levels for which we have also identified effective approaches for overcoming them. Due to limited teachers’ training in sSA, provisions of simple but detailed facilitators’ manual together with supportive supervisions may be critical in ensuring delivery fidelity. During evaluation, computerised audio devices and qualitative interviews with participant observations may facilitate collection and improve validity of adolescents’ sexual behaviours data respectively.

Conclusion Using insights from experiences of researchers, recommendations for developers, implementers or evaluators of SBSHI in sSA that will complement available guidance are provided.